ALXR agonist compound
The present invention provides a compound having ALXR agonist activity. Specifically, the invention provides a compound having ALXR agonist activity represented by general formula (I) wherein all the symbols are as defined in the specification, a salt thereof, a solvate thereof, or a prodrug thereof as well as an agent containing the same as an active ingredient for preventing and/or treating an ALXR-associated disease, such as an inflammatory bowel disease, an autoimmune disease, a chronic inflammatory disease, asthma, pulmonary fibrosis, atopic dermatitis, ischemia-reperfusion injury, myocardial infarction, or Alzheimer's disease.
1. A compound of the following formula (I), or a salt thereof:
wherein
A is a bond, —C(═O)—, —(C(R 5 ) 2 ) m —, —CH═CH—, or —C(═O)NH— (wherein R 5 is a hydrogen atom, a hydroxyl group, a methoxy group, or an ethoxy group, and m is an integer of 1 or 2),
ring L is a phenyl group,
R 1 is a pyridyl group optionally substituted with one to three Ys wherein Y is a hydroxyl group, a halogen atom, a cyano group, a C 1-4 alkyl group, a C 1-4 alkoxy group, or a phenoxy group,
R 2 is a hydrogen atom, a C 1-3 alkyl group, a cyano group, —(C(R 6 ) 2 ) p OH wherein R 6 is a hydrogen atom or a methyl group, and p is an integer of 1 or 2, or —(CH 2 ) q COR 7 wherein R 7 is a hydroxyl group, a methyl group, an amino group, a methoxy group, or an ethoxy group, and q represents an integer of 0 or 1,
R 3 is a hydrogen atom, a hydroxyl group, a halogen atom, a C 1-4 alkyl group, a cyano group, or —NHR 8 wherein R 8 is a hydrogen atom, an acetyl group, or a methylsulfonyl group, and
R 4 is a hydroxyl group, a halogen atom, a C 1-4 alkyl group, or an amino group, and
n is an integer of 0 to 3,
with the proviso that a plurality of Ys, R 4 s, R 5 s, and R 6 s may be the same or different, respectively.
2. The compound according to claim 1 , wherein A is a bond, or a salt thereof.
3. The compound according to claim 1 , wherein R 3 is a hydrogen atom or a hydroxyl group, or a salt thereof.
4. The compound according to claim 1 , wherein R 2 is a hydrogen atom, a methyl group, or —CH 2 OH, or a salt thereof.
5. The compound according to claim 1 , wherein R 1 is a pyridyl group optionally substituted with one Y, or a salt thereof.
6. The compound according to claim 1 , wherein n is 0, or a salt thereof.
7. The compound according to claim 1 , wherein the compound of the formula (I) is represented by the following formula (I-1):
wherein
R 1-1 is a pyridyl group optionally substituted with one Y,
ring L 1 is a phenyl group wherein the ring L 1 is not substituted except for trifluoromethyl group and —NH— group attached thereto,
R 2-1 is a hydrogen atom or a methyl group,
R 3-1 is a hydrogen atom or a hydroxyl group, and
other symbols are as defined in claim 1 ,
or a salt thereof.
8. The compound according to claim 7 , wherein in the formula (I-1), the formula
or a salt thereof.
9. The compound according to claim 8 , wherein the compound of the formula (I-1) is
4-[4-(3-pyridyl)-1,3-thiazol-2-yl]-N-[4-(trifluoromethyl)phenyl]-1-piperidinecarboxamide, or a salt thereof.
10. A pharmaceutical composition comprising a compound represented by general formula (I) as defined in claim 1 , or a salt thereof as an active ingredient, and an inert carrier.